Combination of intermittent haemodialysis and high-volume continuous haemofiltration for the treatment of severe metformin-induced lactic acidosis.

Sir, Metformin has been used for many decades as an effective glucose-loweringmedication in the treatment of type 2 diabetes mellitus. Recentstudies clearly demonstrated that metformin reduced secondarycomplications of diabetes mellitus type 2 without promotingweight gain, which is in contrast to treatment with insulinand/or sulphonylurea [1]. Lactic acidosis is a serious sideeffect observed with metformin treatment and     

The effect of major railway accidents on the psychological health of train drivers—I. Acute psychological responses to accident

The acute psychological reactions of 101 train drivers to on-the-track accidents were studied by means of clinical interviews and questionnaires (Impact of Event Scale, GHQ-20 and a questionnaire addressing stress symptoms, pre-accident expectancies and worries). More than half of the train drivers reported moderate to high intrusive distress (mean 11.3) within hours to days after the accident but only 1/3 reported symptoms of acute psychophysiological arousal. Intrusive symptoms related to visual impressions were most frequently reported. Avoidance was less prevalent (mean 8.8).

Clinical interviews, relationship between pre-accident worries and severity of the acute responses and positive correlation between GHQ-scores relating to the fortnight preceding the accident and IES-intrusion scores, suggest that premorbid variables may influence the stress response. Involvement in more than two previous accidents invoked a feeling of vulnerability and produced stronger acute responses. Post-accident experiences involving various personal contacts did not correlate with the stress responses in this study and only a few drivers experienced such events in a negative way. Denial of the possibility of being involved in accidents was not associated with increased risk of strong acute responses, indicating that denial does not predict poor outcome in healthy persons exposed to situations where possibility of avoiding the event is outside the control of the person.     

Increase in rat brain glutathione following intracerebroventricular administration of gamma-glutamylcysteine.

The effects of intracerebroventricularly (i.c.v.) administered gamma-glutamylcysteine (gamma-GC) and glutathione (GSH) monoethyl ester, subcutaneously (s.c.) injected L-2-oxo-4-thiazolidinecarboxylic acid (OTC) and intraperitoneally (i.p.) administered cysteine on the concentration of GSH in rat brain were investigated. The brain content of GSH, cysteine and gamma-GC was determined by HPLC with electrochemical detection (gold/mercury electrode) using N-acetylcysteine as internal standard. A dose-dependent increase in the GSH concentration (145-170% of controls) was found in the substantia nigra (SN) and in the rest of the brain stem after injection of gamma-GC, whereas no significant alterations in GSH were observed in the striatum and in the cerebral cortex. High levels of gamma-GC could be detected in the brain tissue after the administration, and the concentration of cysteine did also increase markedly after gamma-GC injection in all brain regions assessed. I.c.v. administration of L-buthionine sulfoximine (L-BSO) reduced the brain concentration of GSH by 50-70% within 24 hr. Injection of gamma-GC 24 hr after L-BSO resulted in an increase in GSH up to control values within 1-3 hr in the SN and the rest of the brain stem, whereas only a slight increase in GSH was observed in the striatum and the cerebral cortex. The concentration of GSH in the striatum and SN did not change after i.p. injection of cysteine, but a slight increase in the GSH concentration in the limbic region was observed. GSH monoethyl ester (i.c.v.) and OTC (s.c.) did not produce any significant increase in the GSH concentration in the brain. When the GSH concentration had been reduced by administration of L-BSO (i.c.v.; 24 hr) subsequent injection of GSH monoethyl ester led to a slight increase in the striatal and limbic GSH levels. These data show that, of the drugs studied, gamma-GC was the most effective in increasing brain GSH. It could thus serve as a valuable tool in future studies regarding metabolism and function of GSH in the brain. The observed difference in the effects of gamma-GC in different brain regions indicate that the brain tissue is not homogeneous with regard to GSH synthesizing capacity.     

Functional analysis of rabbit anti-peptide antibodies which mimic autoantibodies against the beta 1-adrenergic receptor in patients with idiopathic dilated cardiomyopathy.

A synthetic peptide corresponding to the second extracellular loop of the beta 1-adrenergic receptor was used as an antigen for antibody production in three rabbits. Antibodies of high titers were obtained in all rabbits. Only one rabbit yielded antibodies which decreased radioligand binding on the receptor in a similar way to that described for autoantibodies in patients with dilated cardiomyopathy. These antibodies recognized the receptor protein in immunoblots. Epitope mapping indicated that the N-terminal sequence of the loop used as antigen was the target of the major antigen fraction. Incubation of antibodies with C6 glioma cell membranes or inner membranes of E. coli, which express the human beta 1-adrenergic receptor, resulted in a decrease in number of radioligand binding sites. This decrease was dependent on the concentration of antibody and of Mg++ ions. It was not affected by the GTP analog GppNHp or the beta 1 subtype-specific antagonist metoprolol. The agonist, isoproterenol, also induced a decrease but the effects of antibody and agonist were not additive. These results suggest that the antibodies induce a Mg(++)-dependent, 'active', labile conformation of the receptor, independent from coupling to the GTP regulatory protein, but similar to that induced by the agonist isoproterenol. This interpretation was corroborated by the beta 1-adrenergic receptor agonist-like effect of the antibodies on cardiomyocytes in culture.     

Predictive power of various models for longitudinal attachment level change

Abstract Several statistical models that have been suggested in the periodontal literature for describing longitudinal attachment level changes, such as the gradual loss, single-burst, multiple-burst, and random walk models as well as other models introduced in this paper are compared by their power to predict future attachment loss. The data used in this analysis is from 1061 sites of 8 subjects, with moderate to severe periodontal disease, monitored monthly for about a year. This study found that none of the suggested models could significantly outperform the naive mean predictor, which predicts the future attachment level from the past mean. It was also found that no single model, such as the burst, gradual, or random walk, together with measurement error can fully explain the variation in the data. These results indicate that in the course of one year, the attachment level change may not follow the same model. Consequently, a model that fits well to past data cannot be accurately extended to the future.     

Receptor binding of N-(methyl-11C) clozapine in the brain of rhesus monkey studied by positron emission tomography (PET)

By means of positron emission tomography the uptake and kinetics of N-(methyl-¹¹C)clozapine in different brain regions have been studied in Rhesus monkeys. ¹¹C-clozapine rapidly entered the brain and maximum radioactive uptake was seen 5–12 min after administration. Highest uptake was measured in the striatum. Other regions with an uptake higher than in the cerebellum were thalamus and mesencephalon. The radioactivity from different brain regions decreased with an elimination half-life of about 5 h and parallelled the plasma kinetics of unlabelled clozapine. The striatum/cerebellum ratio of ¹¹C-clozapine-derived radioactivity remained constant during the period studied and did not change after pretreatment with atropine. In contrast, the striatum/cerebellum ratio was somewhat lower after pretreatment with N-methylspiperone (NMSP), indicating competition for the same binding sites in the striatum. After pretreatment with increasing doses of clozapine, a dose-dependent protection of binding sites in the striatum for ¹¹C-NMSP was seen. It is concluded that clozapine is more loosely bound to dopamine receptors in the striatum than N-methylspiperone and that the kinetics of clozapine in the brain parallel that in the plasma. The binding properties of clozapine within the brain may explain some of the clinical properties of the drug.     

In vitro growth characteristics of human odontogenic keratocysts and dentigerous cysts

Using an in vitro system, the growth characteristics and enzyme histochemical properties of 3 odontogenic keratocysts and 3 dentigerous cysts were studied. It was found that the epithelial cells of the keratocysts hut not of the dentigerous cysts grew in vitro. Furthermore, the epithelial-like cells of the keratocysts showed the same activities of acid phosphatase and NADH-diaphorase in vitro as earlier described in vivo. These enzymatic activities were increased in epithelial-like cells close to proliferating fibroblast-like cells, indicating a close relationship between these two cell types. The results are discussed in the light of the known clinical behaviour of the keratocysts and certain conclusions are also drawn concerning the suggested neo plastic potential of the keratocysts.     

Homozygosity for the transthyretin-Met30-gene in seven individuals with familial amyloidosis with polyneuropathy detected by restriction enzyme analysis of amplified genomic DNA sequences

Familial amyloidotic polyneuropathy (FAP) with a mutation in position 30 of transthyretin (TTR) (previously called prealbumin) is an autosomal dominant inherited disorder characterized by varying degrees of peripheral neuropathy, nephropathy, gastrointestinal problems, and vitreous amyloid. We have earlier diagnosed homozygosity for the TTR-Met30-gene using Southern analysis in four Swedish individuals. We have found it possible to detect homozygosity for the Met-30 mutation by amplifying discrete regions of the TTR-gene using polymerase chain reaction (PCR), and the amplification products restricted with NsiI analysed by gel electrophoresis. Clinical data on seven homozygous individuals, including three new cases, are presented.     

The economics of general thromboembolic prophylaxis

The clinical and economic effects of each of 3 alternatives—no prophylaxis, general prophylaxis, and selective treatment—have been assessed in conjunction with 3 types of surgery—general surgery, the subset surgery for cholelithiasis, and elective hip surgery. The costs of thromboembolic and hemorrhagic complications have been calculated from the figures for 28 patients hospitalized at the Department of Surgery, Malmö General Hospital, Malmö, Sweden. The anticipated number of thromboembolic complications—and thus even the number of fatal pulmonary embolisms—can be minimized in all 3 types of surgery by means of general prophylaxis. General prophylaxis with low-dose heparin is, however, accompanied by the greatest incidence of hemorrhagic complications. Health care costs are minimized with general prophylaxis in elective hip and general surgery, while no prophylaxis is the best alternative in surgery for cholelithiasis. From the patient's point of view, general prophylaxis minimizes the duration of thromboembolic disease in general surgery as well as in elective hip surgery. In surgery for cholelithiasis, however, no differences in health loss for the individual are shown between the 2 main alternatives, no prophylaxis and general prophylaxis. Selective treatment means treatment after diagnosis of thrombosis with some screening method. The alternative selective treatment was the least satisfactory of those 3 studied.

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Resumen Los efectos clínicos y económicos de cada una de 3 alternatives en la profilaxis tromboembólica (no profilaxis, profilaxis general con heparina de baja dosis, y tratamiento selectivo) fueron valorados en 3 tipos de cirugía: cirugía general (abdominal), el subgrupo de cirugía general para colelitiasis, y cirugía electiva de cadera. Los costos de las complicaciones tromboembólicas y hemorrágicas fueron calculados a partir de las cifras observadas en 28 pacientes hospitalizados en el Departmento de Cirugía. El número de predicción de complicaciones tromboembólicas, y el número de embolismos pulmonares fatales pueden ser minimizados en los 3 tipos de cirugía mediante la profilaxis general. Sin embargo, la profilaxis general con heparina de baja dosis se acompaña de la más alta incidencia de complicaciones hemorrágicas.Los costos de la atención pueden ser minimizados mediante la profilaxis general en cirugía electiva de cadera y en cirugía general abdominal, en tanto que la no profilaxis es la mejor alternativa para la cirugía de colelitiasis.Desde el punto de vista del paciente, la profilaxis general minimiza la duración de la enfermedad tromboembólica en la cirugía general abdominal así como en la cirugía electiva de cadera. En la cirugía para colelitiasis, sin embargo, no se demuestran diferencias entre las dos alternatives principales, no profilaxis y profilaxis general.El tratamiento selectivo significa tratamiento una vez establecido el diagnóstico de trombosis mediante algún método de tamizaje. La alternativa de tratamiento selectivo fue la menos satisfactoria de las 3 alternatives estudiadas.

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Résumé Les effets cliniques et financiers de 3 comportements variables: absence de prophylaxie, prophylaxie, traitement sélectif ont été évalué en fonction de trois types de chirurgie: chirurgie générale, chirurgie spéciale de la lithiase biliaire, chirurgie élective de la hanche. Les coûts des complications thrombo-emboliques et hémorragiques ont été calculés à partir des données numériques concernant 28 malades hospitalisés dans le service de chirurgie. Le nombre envisagé des complications thromboemboliques et par conséquent le nombre d'embolie pulmonaire fatale a été réduit dans les 3 types de chirurgie choisis grâce au traitement prophylactique. Cependant il convient de noter que le traitement prophylactique à l'aide de faible dose d'héparine s'accompagne de complications hémorragiques plus nombreuses.Les coûts des soins de la chirurgie élective de la hanche et de la chirurgie générale sont réduits grâce au traitement prophylactique alors que l'absence de traitement prophylactique représente la meilleure modalité à observer dans le traitement de la chirurgie biliaire.En ce qui concerne le point de vue du malade le traitement prophylactique réduit la durée de la maladie thromboembolique compliquant la chirurgie générale ou la chirurgie de la hanche. En revanche dans la chirurgie de la lithiase biliaire aucun inconvénient pour la santé du malade ne s'observe que le traitement prophylactique soit ou ne soit pas appliqué.Le traitement sélectif qui répond au traitement institué après que le diagnostic ait été posé par des méthodes de dépistage est la moins satisfaisante des trois attitudes envisagées.

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Supported by grant no. 00759 from the Swedish Medical Research Council.     

Infantile autism—fragile X: Molecular findings support genetic heterogeneity

Twenty-two members of 18 families with autism have been examined for the presence of mutations and abnormal methylation in the FMR-1 region at Xq27.3. All patients fulfilled diagnostic criteria of infantile autism. A characteristic pattern of insertion and methylation were detected after Southern blot analysis in 7 autistic individuals expressing the fragile site at Xq27.3. Normal DNA patterns were observed in 15 autistic boys cytogenetically negative for the fragile site. The results indicate a lack of involvement of the FMR-1 region in infantile autists negative for fragile X expression. © 1992 Wiley-Liss, Inc.